PGC-1α, a potential therapeutic target against kidney aging

Aging is defined as changes in an organism over time. The proportion of the aged population is markedly increasing worldwide. The kidney, as an essential organ with a high energy requirement, is one of the most susceptible organs to aging. It is involved in glucose metabolism via gluconeogenesis, glucose filtration and reabsorption, and glucose utilization. Proximal tubular epithelial cells (PTECs) depend on lipid metabolism to meet the high demand for ATP. Recent studies have shown that aging-related kidney dysfunction is highly associated with metabolic changes in the kidney. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), a transcriptional coactivator, plays a major role in the regulation of mitochondrial biogenesis, peroxisomal biogenesis, and glucose and lipid metabolism. PGC-1 alpha is abundant in tissues, including kidney PTECs, which demand high energy. Many in vitro and in vivo studies have demonstrated that the activation of PGC-1 alpha by genetic or pharmacological intervention prevents telomere shortening and aging-related changes in the skeletal muscle, heart, and brain. The activation of PGC-1 alpha can also prevent kidney dysfunction in various kidney diseases. Therefore, a better understanding of the effect of PGC-1 alpha activation in various organs on aging and kidney diseases may unveil a potential therapeutic strategy against kidney aging.